Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies

Abstract

SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued suboptimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.

Fig. 1. Serological responses to SARS-CoV-2 vaccination in patients with haematological malignancies.

A Anti-S antibody titres following 1, 2 and 3 vaccines dose in patients, and following 1 and 2 in healthy controls, bar denotes median. B Heatmap showing the percentage of patients with detectable anti-S antibodies (>7.1 BAU/ml) and antibody response greater than the bottom 10% of the antibody range (>568 BAU/ml) stratified by disease type. C Heatmap stratified by treatment. BAU binding antibody units, MDS myelodysplastic syndrome, CLL chronic lymphocytic leukaemia, PTLD post-transplant lymphoproliferative disorder, MPN myeloproliferative neoplasm, ET essential thrombocythemia, PV polycthaemia vera, BTKi burton tyrosine kinase inhibitor, Chemo cytotoxic chemotherapy, JAKi Jak-stat inhibitor, PTx post allogeneic stem cell transplant, TKI tyrosine kinase inhibitor, R/O rituximab or obinotuzumab. Paired analysis by Mann–Whitney U test (two sided).